Cognitive ImpairmentPhase 1NCT02570997
Ascending Dose Study of CT1812 in Healthy Volunteers
A Phase 1 study testing CT1812 in people with Cognitive Impairment, run by Cognition Therapeutics at 1 site in Australia.
Trial summary
This is a double-blind, placebo controlled, ascending dose, multi-cohort trial. The study will be conducted in two phases: a single ascending dose (SAD) phase "Part A", followed by a multiple ascending dose (MAD) phase "Part B". In Part A, subjects will receive one dose of study drug. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Impairment
- What is being tested?
- CT1812
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteAustralia
- Study dates
- Sep 2015to May 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent prior to initiation of any study-related procedures.
- Men and women either ≥ 18 and ≤ 55 years of age or ≥ 65 and ≤75 years of age, depending on cohort.
- In good health as determined by medical history, physical exam, laboratory examinations, ECG, and vital signs.
- BMI between 19 and 34 kg/m2, inclusive.
- Weight between 50 and 100 kg, inclusive.
- ECG without clinically significant pathologic abnormalities and with QTcB <450.
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- Normotensive as defined by systolic BP ≤ 150 mmHg and diastolic BP ≤ 90 mmHg.
- Non-smokers.
- No suicidal ideation, as demonstrated by a score of "0" on the Columbia Suicide Severity Rating Scale (C-SSRS). Part B Only.
- Women who are neither pregnant (negative pregnancy test) nor nursing, and are either surgically sterile or postmenopausal.
Who cannot join
- Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment that might increase the risk to the subject or confound interpretation of safety observations.
- Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
- Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
- History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
- Seropositive for human immunodeficiency virus (HIV).
- History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for Hepatitis B surface antigen [HbsAg] or anti-Hepatitis C [HCV] antibody).
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- Clinically significant abnormalities in specified screening laboratory tests
- All prescription, over-the-counter and herbal medications are prohibited within 10 days prior to study dosing (with exception of calcium/vitamin D supplements, nasal steroids, ocular medications, and paracetamol at the discretion of the Investigator).
- Use of an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing in this study.
- Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs.
- Psychiatric history of current or past psychosis, bi-polar disorder, clinical depression, or anxiety disorder requiring chronic medication within the past 5 years.
- History of substance abuse.
- History of substance or drug dependence or positive urine drug screen at screening visit.
- History of head injury.
- Chronic kidney disease.
- Signs of dementia or cognitive impairment in the elder cohorts.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Two-Part, Double-Blind, Placebo-Controlled, Phase I Study of the Safety Pharmacokinetics of Single and Multiple Ascending Doses of CT1812 in Healthy Volunteers
This is a double-blind, placebo controlled, ascending dose, multi-cohort trial. The study will be conducted in two phases: a single ascending dose (SAD) phase "Part A", followed by a multiple ascending dose (MAD) phase "Part B". In Part A, subjects will receive one dose of study drug. In Part B, subjects within a cohort will receive the same dose daily for 14 days. In both parts, sequential cohorts will be exposed to increasing doses of CT1812 in order to identify the maximum tolerated dose (MTD).
Read the detailed description
Part A - Single Ascending Dose in up to 54 Subjects
Screening procedures will occur on Days -21 to -3. Subjects will be admitted to the clinical research unit for up to 5 days. Administration of a single dose of study drug will occur on Day 1. Following completion of all safety assessments and blood draws for PK analyses, subjects will be discharged on Day 3 or Day 4, depending on cohort.
Double-blind dosing will occur in cohorts 1 through 6. In these cohorts, 6 subjects will receive CT1812 and 2 will receive placebo. Doses will be escalated per protocol.
In cohort 1 only, 2 subjects (1 placebo/1 active CT1812) will be dosed 24 hours prior to the remaining subjects in the cohort. The remaining 6 subjects will be dosed if no safety concerns are identified in the first 2 subjects (the last 6 subjects will be admitted to the research unit one day later than the initial 2 subjects). In cohorts 2 through 7, all subjects will be enrolled and dosed together.
Following completion of each cohort, bioanalytical analyses for CT1812 PK will be performed and plasma Cmax concentrations will be reviewed. Enrollment of additional cohorts and dose escalations will not occur until safety assessments and PK analyses have been completed in the prior cohort.
The dose escalation plan may be adjusted in response to pharmacokinetic analyses, particularly if the relationship between dose and Cmax becomes non-proportional. If an MTD or a maximum allowable exposure is established at less than 650 mg (~8.45 mg/kg), fewer cohorts may be required, reducing the number of study subjects. Should an MTD not be identified (i.e. all doses are well tolerated and review of PK analyses reveal no clinical concerns), additional cohorts at higher doses may be enrolled. The maximum dose administered will not exceed 1350 mg (~18 mg/kg).
At the completion of dose escalation, one additional cohort of 6 subjects will be administered open-label CT1812 at the highest well-tolerated dose or potential therapeutic dose, 30 minutes following a standardized meal to test for food effects.
All subjects will be admitted to the clinical research unit on Day 0. Dosing will take place on the morning of Day 1. Blood draws for assessment of PK parameters will occur pre-dose and at 15, 30, 45, 60, and 90 minutes post dose as well as at 2, 3, 4, 8, 12, 24, 36 and 48 hours post dose. Subjects in cohorts 5 and 6 will have an additional sample drawn 72 hours after dosing. Subjects will be released on Day 3 or 4 following completion of all blood draws and safety assessments.
Part B - Multiple Ascending Dose in up to 60 Subjects
Following identification of the MTD in Part A and analysis of the pharmacokinetic data from Part A, the multiple ascending dose Part B will commence in 4 cohorts.
Screening procedures will occur on Days -21 to -3. Subjects will be admitted to the clinical research unit for 17 days. Once daily administration of study drug will be initiated at 25% of the MTD established in Part A. Dosing will occur on Days 1 - 14. Following completion of all safety assessments and blood draws for PK analyses, subjects will be discharged on Day 16.
In cohorts 3 and 4 only, subjects will undergo lumbar puncture and CSF sampling for CT1812 concentration analysis (single-point) at the steady state Tmax (time after dosing TBD).
In addition to cohorts 1-4, two cohorts of subjects aged 65 to 75 may be enrolled and dosed following identification of the multiple-dose MTD.
- Conditions
- Cognitive Impairment
- Being tested
- CT1812, Placebo
- Keywords
- Alzheimer's Disease, Mild Cognitive Impairment
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CT1812Drug
Also called Study drug
Doses will be escalated in the following sequence: 10mg, 30mg, 90mg, 180mg, 360mg, 650mg.
PlaceboDrug
Matching placebo administered.
| Study group | Role | What they receive |
|---|---|---|
| CT1812 | Active comparator | In cohorts 1-6, 8 subjects will be enrolled. 6 subjects will receive CT1812. Doses will be escalated in the following sequence: 10mg, 30mg, 90mg, 180mg, 360mg, 650mg.
Should an MTD not be identified, additional cohorts at higher doses may be enrolled. The maximum dose administered will not exceed 1350mg. Receives: Drug: CT1812 |
| Matching Placebo | Placebo comparator | In cohorts 1-6, 8 subjects will be enrolled. 6 subjects will receive matching placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and review of Treatment Emergent Adverse Events [Safety and Tolerability]
Treatment Emergent Adverse Events will be assessed by reviewing:
- physical examinations,
- monitoring vital signs,
- monitoring clinical and laboratory assessments,
- monitoring ECGs.
Measured: up to 35 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2015 (estimated)
- Study startSep 2015
- Primary completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cognition Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jason Lickliter, MD, Principal investigator, Nucleus Network Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02570997
- Sponsor's protocol ID
- Cog 0101
- Status last verified
- Oct 2015
- First submitted
- 28 Sep 2015
- Last updated
- 7 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Part, Double-Blind, Placebo-Controlled, Phase I Study of the Safety Pharmacokinetics of Single and Multiple Ascending Doses of CT1812 in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02570997
- Acronym / sponsor ID
- Cog 0101
- Conditions
- Cognitive Impairment
- Keywords
- Alzheimer's Disease, Mild Cognitive Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Cognition TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Sep 2015
- Primary completion
- May 2016 (actual)
- First posted
- 8 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double-blind, placebo controlled, ascending dose, multi-cohort trial. The study will be conducted in two phases: a single ascending dose (SAD) phase "Part A", followed by a multiple ascending dose (MAD) phase "Part B". In Part A, subjects will receive one dose of study drug. In Part B, subjects within a cohort will receive the same dose daily for 14 days. In both parts, sequential cohorts will be exposed to increasing doses of CT1812 in order to identify the maximum tolerated dose (MTD).
Detailed description
Part A - Single Ascending Dose in up to 54 Subjects
Screening procedures will occur on Days -21 to -3. Subjects will be admitted to the clinical research unit for up to 5 days. Administration of a single dose of study drug will occur on Day 1. Following completion of all safety assessments and blood draws for PK analyses, subjects will be discharged on Day 3 or Day 4, depending on cohort.
Double-blind dosing will occur in cohorts 1 through 6. In these cohorts, 6 subjects will receive CT1812 and 2 will receive placebo. Doses will be escalated per protocol.
In cohort 1 only, 2 subjects (1 placebo/1 active CT1812) will be dosed 24 hours prior to the remaining subjects in the cohort. The remaining 6 subjects will be dosed if no safety concerns are identified in the first 2 subjects (the last 6 subjects will be admitted to the research unit one day later than the initial 2 subjects). In cohorts 2 through 7, all subjects will be enrolled and dosed together.
Following completion of each cohort, bioanalytical analyses for CT1812 PK will be performed and plasma Cmax concentrations will be reviewed. Enrollment of additional cohorts and dose escalations will not occur until safety assessments and PK analyses have been completed in the prior cohort.
The dose escalation plan may be adjusted in response to pharmacokinetic analyses, particularly if the relationship between dose and Cmax becomes non-proportional. If an MTD or a maximum allowable exposure is established at less than 650 mg (~8.45 mg/kg), fewer cohorts may be required, reducing the number of study subjects. Should an MTD not be identified (i.e. all doses are well tolerated and review of PK analyses reveal no clinical concerns), additional cohorts at higher doses may be enrolled. The maximum dose administered will not exceed 1350 mg (~18 mg/kg).
At the completion of dose escalation, one additional cohort of 6 subjects will be administered open-label CT1812 at the highest well-tolerated dose or potential therapeutic dose, 30 minutes following a standardized meal to test for food effects.
All subjects will be admitted to the clinical research unit on Day 0. Dosing will take place on the morning of Day 1. Blood draws for assessment of PK parameters will occur pre-dose and at 15, 30, 45, 60, and 90 minutes post dose as well as at 2, 3, 4, 8, 12, 24, 36 and 48 hours post dose. Subjects in cohorts 5 and 6 will have an additional sample drawn 72 hours after dosing. Subjects will be released on Day 3 or 4 following completion of all blood draws and safety assessments.
Part B - Multiple Ascending Dose in up to 60 Subjects
Following identification of the MTD in Part A and analysis of the pharmacokinetic data from Part A, the multiple ascending dose Part B will commence in 4 cohorts.
Screening procedures will occur on Days -21 to -3. Subjects will be admitted to the clinical research unit for 17 days. Once daily administration of study drug will be initiated at 25% of the MTD established in Part A. Dosing will occur on Days 1 - 14. Following completion of all safety assessments and blood draws for PK analyses, subjects will be discharged on Day 16.
In cohorts 3 and 4 only, subjects will undergo lumbar puncture and CSF sampling for CT1812 concentration analysis (single-point) at the steady state Tmax (time after dosing TBD).
In addition to cohorts 1-4, two cohorts of subjects aged 65 to 75 may be enrolled and dosed following identification of the multiple-dose MTD.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CT1812 | Active comparator | Drug: CT1812In cohorts 1-6, 8 subjects will be enrolled. 6 subjects will receive CT1812. Doses will be escalated in the following sequence: 10mg, 30mg, 90mg, 180mg, 360mg, 650mg. Should an MTD not be identified, additional cohorts at higher doses may be enrolled. The maximum dose administered will not exceed 1350mg. |
| Matching Placebo | Placebo comparator | Drug: PlaceboIn cohorts 1-6, 8 subjects will be enrolled. 6 subjects will receive matching placebo. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Willing and able to provide written informed consent prior to initiation of any study-related procedures.
- Men and women either ≥ 18 and ≤ 55 years of age or ≥ 65 and ≤75 years of age, depending on cohort.
- In good health as determined by medical history, physical exam, laboratory examinations, ECG, and vital signs.
- BMI between 19 and 34 kg/m2, inclusive.
- Weight between 50 and 100 kg, inclusive.
Key exclusion criteria (16 listed)
- Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment that might increase the risk to the subject or confound interpretation of safety observations.
- Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
- Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
- History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
- Seropositive for human immunodeficiency virus (HIV).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CT1812Also: Study drugDoses will be escalated in the following sequence: 10mg, 30mg, 90mg, 180mg, 360mg, 650mg. | Drug | CT1812 |
| PlaceboMatching placebo administered. | Drug | Matching Placebo |
Primary outcome
Incidence and review of Treatment Emergent Adverse Events [Safety and Tolerability]
Time frame: up to 35 days
Treatment Emergent Adverse Events will be assessed by reviewing: * physical examinations, * monitoring vital signs, * monitoring clinical and laboratory assessments, * monitoring ECGs.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Lickliter, MD principal investigator
Nucleus Network Ltd
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CT1812 in people with Cognitive Impairment, run by Cognition Therapeutics at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and review of Treatment Emergent Adverse Events [Safety and Tolerability] (time frame: up to 35 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2016.